01/22/2015

Outline

  • PHQchange Variable

  • Association Tests

    - PHQchange ~ Baseline Methylation
- INT PHQchange ~ Baseline Methylation
- PHQchange ~ Difference in Methylation
- INT PHQchange ~ Difference in Methylation

  • Correlation Analysis

    - PHQchange ~ Difference in Methylation
  • Paired Tests on Methylation between visits
  • Simplex Regression

  • Data Summary

PHQ Change

    min      q1  median    mean      q3     max      sd       n 
 -19.00    1.00    2.81    3.25    5.00   24.00    3.72 1865.00

Transformation of PHQ change

Asso. of PHQchange ~ Baseline Methylation

  • Goal : To identify baseline DNA methylation markers that predict the change in PHQ (Aim 1)

  • Model : PHQchange = a + b * BaselineMethylation + e

  • Sites : 485512

  • Sample size: 65

  • Multiple Testing Correction : Bonferroni

  • 5% MinP Cutoff - Raw PHQchange : 1.36e-08

  • 5% MinP Cutoff - INT PHQchange : 1.43e-08

QQplot of pvals from Model (Genome wide)

QQplot of pvals based on Raw PHQchange and CI

Results based on Raw PHQchange
CpG Chr Genes Pos beta pval p.adj size
cg25660390 17 NA 73073700 0.003 0e+00 0.0043 65
cg22577606 7 CYP51A1 91763103 0.010 1e-07 0.0268 65
cg07219643 12 WSB2 118499016 0.001 1e-07 0.0363 65
cg15286044 10 CRTAC1 99789971 0.004 1e-07 0.0424 65
cg23932859 5 MEGF10 126625777 0.008 2e-07 0.1098 65
cg23679073 2 ZC3H15 187350909 0.002 3e-07 0.1563 65
cg26752884 11 JRKL;CCDC82 96123217 0.002 4e-07 0.2001 65
cg04992638 17 LOC100133991;C17orf46 43339328 0.002 4e-07 0.2098 65
cg05795554 16 FANCA 89883212 0.004 8e-07 0.3777 65
cg25365565 6 HIST1H2BJ;HIST1H2AG 27101050 0.001 1e-06 0.4974 65

Studentized Residual QQ plots top 6 sites - raw PHQchange

Leverage Plots top 6 sites - raw PHQchange

Cook's Distance

QQplot of pvals based on INT PHQchange and CI

Results based on INT PHQchange
CpG Chr Genes Pos beta pval p.adj size
cg07219643 12 WSB2 118499016 0.004 1.0e-07 0.0566 65
cg23679073 2 ZC3H15 187350909 0.008 1.0e-07 0.0639 65
cg15286044 10 CRTAC1 99789971 0.013 7.0e-07 0.3271 65
cg00220389 17 NA 80455521 0.006 7.0e-07 0.3462 65
cg07696033 11 ALX4 44326410 0.008 1.1e-06 0.5174 65
cg20696752 17 LSM12 42143797 0.004 1.5e-06 0.7459 65
cg14613271 2 SLC5A7 108602931 0.013 2.2e-06 1.0000 65
cg02592615 6 HIVEP1 12012261 0.010 2.5e-06 1.0000 65
cg07399094 6 NA 3163461 0.007 2.9e-06 1.0000 65
cg26752884 11 JRKL;CCDC82 96123217 0.006 3.0e-06 1.0000 65

Residual QQ plots top 6 sites - INT transformed

Leverage Plots top 6 sites - INT PHQchange

Cook's Distance

Asso. of PHQchange ~ Difference in Methylation

  • Goal : To identify DNA methylation markers which the difference in methylation are associated with change in PHQ (~ Aim 2)

  • Model : PHQchange = a + b * MethylationDifference + e

  • Sites : 485512

  • Sample size: 37

  • Multiple Testing Correction : Bonferroni

  • 5% MinP Cutoff - raw PHQchange: 5.16e-09

  • 5% MinP Cutoff - INT PHQchange: 1.38e-08

QQplot of pvals from Model (Genome wide)

QQplot of pvals based on Raw PHQchange and CI

Results based on Raw PHQchange
CpG Chr Pos Genes pval p.adj size
cg00886598 5 42812844 SEPP1 2.0e-07 0.0850 37
cg20292653 2 5847374 NA 2.0e-07 0.1151 37
cg05518543 4 1283165 MAEA 3.0e-07 0.1423 37
cg20049415 20 21377671 NKX2-4 8.0e-07 0.3751 37
cg07432626 5 146889536 NA 1.0e-06 0.4990 37
cg10059942 10 124908488 HMX2 3.6e-06 1.0000 37
cg10169763 16 87873389 SLC7A5 4.4e-06 1.0000 37
cg03625512 12 125569850 AACS 4.4e-06 1.0000 37
cg24601967 1 6366496 ACOT7 5.4e-06 1.0000 37
cg07678449 4 171011395 AADAT 6.5e-06 1.0000 37

Residual QQ plots top 6 sites - raw PHQchange

Leverage Plots top 6 sites - raw PHQchange

Cook's Distance

QQplot of pvals based on INT PHQchange and CI

Results based on INT PHQchange
CpG Chr Pos Genes pval p.adj size
cg20292653 2 5847374 NA 4.00e-07 0.194 37
cg05706582 7 2566911 LFNG 5.50e-06 1.000 37
cg09640960 20 60794676 HRH3 7.00e-06 1.000 37
cg23026478 6 46706037 NA 1.03e-05 1.000 37
cg00886598 5 42812844 SEPP1 1.28e-05 1.000 37
cg10169763 16 87873389 SLC7A5 1.55e-05 1.000 37
cg09405169 3 12329745 PPARG 3.26e-05 1.000 37
cg14912788 1 3661862 KIAA0495 3.41e-05 1.000 37
cg13883397 11 61900852 INCENP 3.49e-05 1.000 37
cg12405983 19 58630240 ZSCAN18 3.69e-05 1.000 37

Residual QQ plots top 6 sites - INT PHQchange

Leverage Plots top 6 sites - INT PHQchange

Cook's Distance

Correlation of PHQchange ~ Difference in Methylation

  • Goal : To identify DNA methylation markers which the difference in methylation are correlated with change in PHQ (~ Aim 2)

  • Method : Spearmen's correlation

  • Sites : 485512

  • Sample size: 37

Diff. in Methylation (6 random Cpg sites)

QQplots of Cor Test

Results of Correlation Test
CpG Chr Genes Pos rho pval size
cg20292653 2 NA 5847374 -0.7185908 5.00e-07 37
cg09640960 20 HRH3 60794676 -0.6884568 2.50e-06 37
cg05706582 7 LFNG 2566911 -0.6708983 5.50e-06 37
cg09405169 3 PPARG 12329745 0.6526281 1.20e-05 37
cg02570593 13 ING1 111366092 0.6520349 1.23e-05 37
cg22749736 11 TOLLIP 1306759 0.6256972 3.45e-05 37
cg23753795 6 GRM1 146531540 0.6208331 4.14e-05 37
cg02582203 11 NA 43604219 -0.6196467 4.32e-05 37
cg23873430 X DCX 110655626 -0.6196467 4.32e-05 37
cg14912788 1 KIAA0495 3661862 0.6149011 5.13e-05 37

Paired T-test QQ-plot

Summary of SimplexReg

Four Simplex Models and %success

  1. simplex(site) ~ time, 77%
  2. simplex(site) ~ time + sex, 78%
  3. simplex(site) ~ time + age, 77%
  4. simplex(site) ~ time + sex + age, 77%

Table of NA Pattern for Simplex Reg

   time.sex.age time.age time.sex time notRun count percent
1             1        1        1    1      0   489   56.60
2             1        0        1    1      1     3    0.35
3             0        1        1    1      1   143   16.55
4             1        1        0    1      1     5    0.58
5             1        1        1    0      1    19    2.20
6             0        0        1    1      2     3    0.35
7             1        0        0    1      2    17    1.97
8             1        0        1    0      2     4    0.46
9             0        1        1    0      2     4    0.46
10            1        1        0    0      2     6    0.69
11            0        0        0    1      3     5    0.58
12            1        0        0    0      3   132   15.28
13            0        1        0    0      3     3    0.35
14            -        -        -    -      -    31    3.59
15          189      195      199  199    782   864  100.00

Dist of V1 on 9 Random sites, ran on all models

Dist of V2 on 9 Random sites, ran on all models

Dist of V1 on 9 Random sites, didn't Run

Dist of V2 on 9 Random sites, didn't Run

Baesline Data Summary

Covariates

  • Baseline covaritates(14)

    Age, Sex, Ethnicity, Specialty, Marital, Child, Clerk, EFE, Neu, SleepAssessment, AlcoholUse

  • Baseline to Q4 (7)

    Hours, Daysoff, Sleep, SleepAvg. Well-being14, StressfulEvents, PHQ

  • Q1 to Q4 only (2)

    Rotation, MentalHealthTreatment

  • Q4 only Covariate (1)

    ResidentExperience17